Set1/Ash2 histone methyltransferase complex subunit ASH2 (UniProt Q9UBL3 & Q91X20; also known as ASH2-like protein) is encoded by the human ASH2L (also known as ASH2L1) and murine Ash2l gene (Gene ID 9070 & 23808). Ash2L is a component of the MLL histone H4 Lys4 (H4K4) methyltransferase complexes composed of Ash2L, RBBP5, WDR5, HDPY-30, one of seven SET/MLL proteins (SETA, SETB, MLL1 to MLL5), and additional MLL complex-specific non-core proteins. For example, the MLL3/4 complex contains the H3K27 demehtylase UTX and the receptor coactivator NCOA6. Ash2L is also present in a complex that contains RbBP5 and Wdr5, but not SET/MLL proteins. Ash2L contains a DNA-binding forkhead-like helix-wing-helix domain (a.a. 67-177 of human and a.a. 63-172 of mouse Ash2L) in its N-terminal region and a B30.2/SPRY (a.a. 360-583 of human and a.a. 355-578 of mouse Ash2L) domain in its C-terminal region involved in protein-protein interactions. Ash2L is reported to interact with AP2G, GATA3, MEF2, and TBX1, and is involved in their transcriptional activation. In addition, p53 induction is shown to cause increased H3K4me3 epigenetic modification at its pro-apoptotic target promoters, resulting in enhanced Wdr5, RbBP5 and Ash2L occupancy at these pro-apoptotic gene promoters. Ash2L overexpression is reported to enhance p53 pro-apoptotic gene expression and p53-dependent apoptosis of cancer cells in response to chemotherapy, while Ash2L silencing abrogates p53-dependent target gene expression.
Synonyms: Set1/Ash2 histone methyltransferase complex subunit ASH2, ASH2-like protein
Application: Research CategoryEpigenetics & Nuclear Function
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